Group II metabotropic glutamate (mGlu) receptors are known to play an important role in regulating the release of excitatory transmitter in a number of brain areas (Schoepp, 2001). Previous experiments in rat barrel cortex suggested that synaptic responses were depressed by the agonist 1S,3R-ACPD (Cahusac, 1994). To further clarify the role of these receptors in cortical somatosensory processing, experiments were done using a more selective receptor agonist and antagonist. Single cell recordings were made from 4 adult urethane anaesthetized (2g/kg I.P.) Wistar-derived rats. Micropipettes were used in which the central barrel contained a carbon fibre for recording action potentials. Surrounding barrels contained combinations of the following: monosodium L-glutamate (0.5 M, pH 8.5), (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 10 mM in 75 mM NaCl, pH 8), GABA (0.5 M, pH 3.5), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 0.1 M, pH 8), (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC, 0.1 M, pH 8), (2S)-α-ethylglutamic acid (EGLU, 0.1 M, pH 10), Pontamine Sky Blue dye (2% in 0.5 M Na acetate) and 1 M NaCl (for current balancing and current controls). Stimuli consisted of brief (3 ms) deflections of the principal vibrissa by a piezoelectric bimorph. The selective Group II receptor agonist 2R,4R-APDC (40 – 100 nA) depressed synaptic transmission in 9 of 20 neurones studied (mean effect was 61 ± 2.4% (S.E.M.) of control responses). In some experiments 2R,4R-APDC (40–100 nA) was studied alongside 1S,3R-ACPD (20–100 nA). No excitatory effects of 2R,4R-APDC were seen, and analyses only include cells which were depressed. The same depressant effects on synaptic responses were seen with both compounds in all 5 cells tested (57 ± 2.1% and 47 ± 9.1%) of control responses, respectively). The synaptic depressant effects observed were selectively antagonised relative to GABA by the selective Group II receptor antagonist EGLU (70–150 nA) in 7 out of 10 cells tested. The interaction between drug and time was statistically significant (F(2,12) = 9.13, p = 0.004), as were the relevant multiple comparisons, which showed that only Group II agonist-produced depressions were antagonised during EGLU. In 2 experiments where selective antagonism by EGLU was achieved, the same Group II agonist currents were used against postsynaptic excitations produced by iontophoretic AMPA. In each case the Group II receptor agonists had little or no effect on the excitations, while GABA had the expected depressant effect. These results are consistent with work in cat visual cortex (Beaver et al. 1999), and provide evidence that Group II mGlu receptors mediate presynaptic depression of excitatory synaptic transmission. Such a role may be important in keeping excitatory activity within certain physiological limits, or may play more specific roles in the coding of different types of somatosensory information in primary sensory cortex.